The proposed research is to define the multipotential retinal precursor cell and mechanisms which regulate the fate choices of this cell into mature neurons and glia. Elucidating this differentiation pathway is important for understanding congenital syndromes of dysgenetic brains, neurogenic tumors and neurodegenerative diseases. The newly identified intermediate filament protein nestin appears to be specific for neuronal and glial precursor cells in many areas of the CNS. The expression of nestin in retinal stem cells will be determined . Once the pathway from a nestin-positive precursor to a mature retinal cell has been delineated in vivo and in vitro, retinal precursor cell lines will be generated and characterized. These cell lines will provide an in vitro system for studying neuronal differentiation. Growth factors, substrates and cell-cell contacts important for guiding the differentiation of neuronal cell will be investigated using these new cell lines.